1. Field of the Invention
The present invention relates generally to methods and apparatus for sterilizing medical buffers and other solutions. More specifically, the present invention relates to methods and devices for holding medical buffers and solutions under pressure while undergoing heat sterilization.
A buffer solution is a solution that tends to change the pH of other solutions with which it comes in contact to the buffer solution's pH. Medical buffer solutions frequently contain bicarbonate ions and are used in numerous medical applications including antidotes, dialysates, body replacement fluids, body irrigating solutions, cardiac perfusates, and for many other purposes. One of the most commonly used medical bicarbonate buffer solutions consists of sodium bicarbonate (NaHCO3) mixed with water, which among other things, can be used to buffer parenteral injections to a more physiologic pH prior to injection. Of particular interest to the present application, bicarbonate solutions may be used to buffer acidic local anesthetic injections in order to enhance anesthetic effectiveness, reduce injection pain, and limit tissue trauma. For use of sodium bicarbonate for buffering local anesthetic, as well as for other medical uses including but not limited to treatment of acidosis, it is desirable that sodium bicarbonate solutions be precisely maintained at or near a particular known pH. Using a buffer solution having a known pH allows a medical practitioner to mix a predetermined ratio of the buffer solution with the parenteral solution in order to achieve control over the resulting pH of parenteral solution, which has significant benefits over using a parenteral solution where the pH is not controlled.
As an example, when compounding 8.4% sodium bicarbonate buffer solution with commercially available cartridges of 2% lidocaine with epinephrine 1:100,000, the pH of the buffer solution will tend to drive the pH of the combination, almost exclusively of the pH of the commercially available anesthetic cartridges, such that a relatively small volume of buffer solution will have a disproportionately large impact on the pH of the combined solution. Thus, to achieve a parenteral solution with a predictable pH, it is important that the pH of the buffer solution be precisely known and controlled, in addition to knowing and controlling the amount of buffering solution to add to the local anesthetic. Only when the pH of the buffer solution being added and the amount of buffer being added are both known can the practitioner know and control the resulting pH of the buffered anesthetic.
Commercially produced sodium bicarbonate buffers do not provide buffer packages with precisely controlled pH. For example, an assay of the commercially available sodium bicarbonate solutions performed by the inventors showed a pH range from 7.62 to 8.26 in a number of commercially obtained bicarbonate buffer cartridges. Presumably the actual range of the product available in the marketplace is even wider than the range identified in this small assay.
It must be appreciated, in this context, that a medical buffer having an actual pH of 7.6 may perform significantly differently than a medical buffer having an actual pH of 8.3. This is true whether the medical buffer is designed to buffer the pH of the body's fluids, for instance in the treatment of acidosis, or the medical buffer is designed to buffer the pH of a parenteral solution prior to its use. In the example where a practitioner uses sodium bicarbonate solution to buffer anesthetic to achieve physiologic pH, the ratio of buffer solution to anesthetic solution will be quite different when the pH of the bicarbonate solution is 7.6 compared to when the pH is 8.3. Thus, prior art methods of combining buffering solution with parenteral solutions which rely on adding the same ratio of buffering solution to the parenteral solution, regardless of the actual pH of the buffer, will not consistently arrive at a desired pH for the buffered parenteral.
A method and system for adjusting the pH of medical buffers and other medical solutions to a precisely controlled value in a plurality of identical buffer cartridges or other containers is described in co pending application Ser. No. 12/766,259, filed on Apr. 23, 2010, the full disclosure of which is incorporated herein by reference. That application teaches that the pH of the solutions in individual containers can be adjusted by exposing those containers, while open, to an environment having a controlled temperature, humidity, pressure, and level of carbon dioxide. After the pH has equilibrated to a target pH, the cartridges can be sealed with no head space remaining within the cartridges. Once the cartridges are sealed, an inventory of cartridges having precisely controlled and identical pH values can be created. The need to sterilize the containers and their contents, however, can adversely affect the contents of the cartridges. Sterilization is typically done at elevated temperatures which can cause the buffer or other medical solution to boil, which can cause the seals to fail or can otherwise adversely impact the solution and the container.
For these reasons, it would be desirable to provide methods and apparatus for sterilizing cartridges and similarly packaged buffer solutions so as to prevent boiling and other adverse changes that might occur during heat sterilization. It would be particularly desirable to be able to sterilize multiple buffer or other medical solution packages simultaneously while holding the packages in trays or other containers that are also suitable for subsequent storage and shipment of the buffers. At least some of these objectives will be met by the inventions described hereinbelow.
2. Description of the Background Art
Glass vials and cartridges for storing medical solutions are described in U.S. Pat. Nos. 1,757,809; 2,484,657; 4,259,956; 5,062,832; 5,137,528; 5,149,320; 5,226,901; 5,330,426; and 6,022,337. Injection pens which employ drug cartridges are described in U.S. Pat. No. 5,984,906. Exemplary disposable drug cartridge that could be loaded with buffer solution in accordance with the present invention are described in U.S. Pat. No. 5,603,695 and in commonly owned, co pending application US2009/0292271 (U.S. Ser. No. 12/406,670), both of which are incorporated herein by reference. A device for delivering a buffering agent into an anesthetic cartridge using a transfer needle is described in U.S. Pat. No. 5,603,695. Devices for maintaining a dissolved gas in solution in a pouch are described in U.S. Pat. Nos. 5,690,215; 5,610,170; and 4,513,015, and U.S. Patent Publ. No. 2007/0265593. Other patents and applications of interest include U.S. Pat. Nos. 2,604,095; 3,993,791; 4,154,820; 4,630,727; 4,654,204; 4,756,838; 4,959,175; 5,296,242; 5,383,324; 5,603,695; 5,609,838; 5,779,357; and U.S. Patent Publ. No. 2004/0175437. Literature publications describing buffering anesthetics with widely different ratios of a sodium bicarbonate solutions include Ridenauer et al., Anesth Prog, vol. 48, p. 9-15 (2000); Palmon et al., Anesth Analg, vol. 86, pp. 379-81 (1998); Metzinger et al., Southern Med J, vol. 87, no. 2 (1994); Nelson, Contracept, vol. 55, p. 299 (1995); Samdal, Scand J Plast and Recons Surg and Hand Surg, vol. 28, p. 33-37 (1993); Master, Br. J Plast Surg, vol. 51, p. 385 (1998); Difazio et al. Anesth Analg, vol. 65, p. 760 (1986); Fitton et al., Br. J Plast Surg, vol. 49, pp. 404-08 (1996); Peterfreund et al., Region Anesth, vol. 14, no. 6, p. 265 (1989); Momsen et al., Ugeskr Laeger, vol. 162, no. 33, p. 4391 (2000); Schwab et al. Am J Emerg Med, vol. no. 3 (1996); McGlone et al. Arch Emerg Med, vol. 7, pp. 65-68 (1990); and Sapin P, et al. Catheterization and Cardio Diag, vol. 23, pp. 100-102 (1991).